The beneficial effects of vortioxetine on BDNF, CREB, S100B, ß amyloid, and glutamate NR2b receptors in chronic unpredictable mild stress model of depression.

BACKGROUND: Depression, one of the most significant mental disorders, is still poorly understood in terms of its pathogenetic mechanisms despite its well-recognized association with stress. OBJECTIVES: The current study's goal was to ascertain how the novel antidepressant drug vortioxetine (VOR) affected the BDNF (brain-derived neurotrophic factor), S100, amyloid ß (Aß), CREB (cAMP response element-binding protein), and NR2B, as well as its impact on depression-like behaviors, and tissue damage in an experimental rodent model of depression caused by chronic unpredictable stress. METHODS: We employed twenty-eight Wistar albino male rats, and we randomly divided them into four groups, each consisting of 7 rats: control, CUMS (chronic unpredictable mild stress), CUMS+vortioxetine (CUMS+VOR), and CUMS+fluoxetine (CUMS+FLU). Sucrose preference and forced swimming tests (SPT and FST, respectively), PCR, ELISA, and histopathological and immunohistochemical evaluation were made on brains. RESULTS: The behaviors of reduced immobility in the FST and increased sucrose preference were observed in the CUMS group and they improved in the groups treated with VOR and FLU. Compared with the control group, the group exposed to CUMS showed increased Aß and decreased BDNF, CREB, and S-100 expressions, as well as neuronal degeneration (p<0.001). VOR and FLU treatment ameliorate the findings. CONCLUSIONS: This study demonstrated significant ameliorative effects of VOR in an experimental model of chronic unpredictable depression to reduce brain tissue damage and depression-like behaviors in rats. Effects of CUMS on the brain and possible effects of VOR.

Ameliorating effects of ramelteon on oxidative stress, inflammation, apoptosis, and autophagy markers in methotrexate-induced cerebral toxicity.

Objectives: Methotrexate (MTX) is a widely used chemotherapeutic agent that, however, is known to have serious side effects such as neurotoxicity. In the present study, we aimed to evaluate the possible favorable effects of ramelteon (RMLT) on MTX-induced cerebral toxicity. Materials and Methods: Thirty-two male Wistar albino rats were divided into four groups: Control group, MTX group (20 mg/kg MTX, IP, single dose), MTX+RMLT group (20 mg/kg MTX, IP, single dose + 10 mg/kg RMLT, by gavage, 7 days), and RMLT group (10 mg/kg RMLT, by gavage, 7 days). Results: In the MTX group, increased levels of total oxidant status (TOS) and oxidative stress index (OSI) levels and decreased levels of total antioxidant status (TAS) level were observed. RMLT significantly reversed oxidative stress parameters. Real-time PCR analysis revealed that MTX increased the expressions of Beclin-1 and autophagy-related gene 12 (ATG12). These expressions were significantly decreased by RMLT. Vacuolar changes, apoptotic cells, and inflammatory cell infiltration induced by MTX were ameliorated by RMLT treatment. Increased tumor necrosis factor-α (TNF- α) and Caspase-3 activities induced by MTX were returned to their normal levels by RMLT. Conclusion: All our results demonstrate that RMLT alleviates the harmful effects of MTX on the cerebral cortex tissue. Therefore, RMLT may be considered for supportive therapy for preventing side effects of MTX in patients needing MTX therapy.

Hypothalamic NR3C1 DNA methylation in rats exposed to prenatal stress.

BACKGROUND: Human and animal studies have indicated that maternal prenatal stress (PS) has molecular and behavioral effects during pregnancy and early life. The present study aimed to evaluate the epigenetic changes of the NR3C1 gene involved in the HPA axis in the hypothalamic tissues of rats exposed to PS induced by chronic unpredictable mild stress (CUMS). Behavioral and molecular effects of these changes on the next generation were also assessed. METHODS AND RESULTS: CUMS protocol was used to generate stress in pregnant Wistar rats. To determine the effects of stress on anhedonia and movement, sucrose preference test, forced swimming test, and open field test were performed. Following these behavioral experiments, bisulfite sequencing PCR for DNA methylation levels of the NR3C1 gene, RT-qPCR for mRNA levels, and Western blot techniques for protein analysis were used in the hypothalamic tissue of sacrificed rats. Depression-like behaviors were evident in the behavioral tests of stress-exposed mothers and pups. In PS-exposed pups, hypothalamic NR3C1 promoter methylation was higher, and NR3C1 mRNA levels and NR3C1 protein levels were lower compared with controls, regardless of sex. CONCLUSION: Our results confirm the relationship between PS and epigenetic changes of HPA axis-related genes and show that NR3C1 gene methylation status in pups is sensitive to PS during pregnancy. Environmental maternal stress may have transgenerational effects that are potentially associated with adverse outcomes in the pups.

The role of oxidant status on the etiopathogenesis of unexplained infertility and intracytoplasmic sperm injection - embryo transfer success: a case-control study.

The present study aims to evaluate the role of follicular fluid (FF) and serum (s) total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) on the etiopathogenesis of unexplained infertility (UI) and intracytoplasmic sperm injection-embryo transfer (ICSI-ET) success. Twenty UI patients and 20 controls with male factor undergoing an ICSI-ET cycle were recruited. FF samples aspirated from mature follicles and blood samples collected just before the oocyte retrieval were stored until analysis. Embriyo quality and implantation, clinical pregnancy and living birth rates were evaluated.FF-TOS and FF-OSI of the UI patients were higher than the control group. s-TOS and s-OSI were significantly increased in the UI group compared to the control group. However, only s-TOS was positively associated with UI diagnosis after age-adjustment. FF-OSI was negatively associated with embryo quality in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI on implantation, clinical pregnancy and live birth rate was observed. In conclusion, especially s-TOS can have a partial role in the etiopathogenesis of UI. High FF-OSI can decrease the quality of embryo in patients with UI.Impact statementWhat is already known? Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), which is the ratio of TOS to TAS, provide a broad overview of redox status.What do the results of this study add? An elevated serum TOS (s-TOS) was associated with UI after age-adjustment. Follicular fluid OSI (FF-OSI) was negatively associated with embryo quality and embryo score in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI was observed on implantation, clinical pregnancy, and live birth rate.What are the implications of these findings for clinical practice and/or further research? Evaluation of FF-OSI in women with unexplained infertility can be considered to predict embryo quality. Further studies that evaluate antioxidant agents to decrease oxidative stress in UI and its' clinical implications are warranted.

Salivary glands of fetuses are adversely affected by artificial food colorings in rats.

OBJECTIVE: Artificial food colorings, as types of food additives, are widely used at present in daily life. We aimed to investigate the effects of exposure to artificial food colorings during the intrauterine period on the salivary glands in adulthood. METHODS: A total of 30 Wistar albino female pregnant rats were included in this study. The treatment group was given a mixture of nine artificial food colorings at no observed adverse-effect-level doses. Neither mothers nor offspring were fed with food colorings after delivery. When the offspring became adults, they were sacrificed, and the possible histopathological and immunohistochemical effects of artificial food colorings on the salivary glands were investigated. In these glands, anti-matrix metallopeptidase 2 (anti-MMP2), anti-MMP9, anti-tissue inhibitor of metalloproteinases (TIMP) metallopeptidase inhibitor 1 (anti-TIMP1), anti-TIMP2, and anti-TIMP3 were examined. RESULTS: The expressions of anti-MMP2, anti-TIMP1, anti-TIMP2, and anti-TIMP3 parameters were found to be higher in treatment groups (p<0.05). CONCLUSION: It was suggested that intrauterine exposure of synthetic food colorings may lead to deterioration of the tissue structure of the salivary glands in adulthood, thereby increasing susceptibility to chronic illnesses including malignancy and chronic inflammation. Therefore, pregnant women should give importance to their nutrition in terms of foods containing synthetic colorings.

Salivary glands of fetuses are adversely affected by artificial food colorings in rats

SUMMARY OBJECTIVE: Artificial food colorings, as types of food additives, are widely used at present in daily life. We aimed to investigate the effects of exposure to artificial food colorings during the intrauterine period on the salivary glands in adulthood. METHODS: A total of 30 Wistar albino female pregnant rats were included in this study. The treatment group was given a mixture of nine artificial food colorings at no observed adverse-effect-level doses. Neither mothers nor offspring were fed with food colorings after delivery. When the offspring became adults, they were sacrificed, and the possible histopathological and immunohistochemical effects of artificial food colorings on the salivary glands were investigated. In these glands, anti-matrix metallopeptidase 2 (anti-MMP2), anti-MMP9, anti-tissue inhibitor of metalloproteinases (TIMP) metallopeptidase inhibitor 1 (anti-TIMP1), anti-TIMP2, and anti-TIMP3 were examined. RESULTS: The expressions of anti-MMP2, anti-TIMP1, anti-TIMP2, and anti-TIMP3 parameters were found to be higher in treatment groups (p<0.05). CONCLUSION: It was suggested that intrauterine exposure of synthetic food colorings may lead to deterioration of the tissue structure of the salivary glands in adulthood, thereby increasing susceptibility to chronic illnesses including malignancy and chronic inflammation. Therefore, pregnant women should give importance to their nutrition in terms of foods containing synthetic colorings.

Serum zonulin and claudin-5 levels in patients with schizophrenia.

The aim of this research was to assess whether or not changes in the concentrations of serum zonulin and claudin-5 in patients with schizophrenia could have etiopathogenetic importance. In previous studies, the data regarding the relationship between intestinal and blood-brain barrier (BBB) permeability and the etiology of schizophrenia have been limited. In this study, we assumed that there may be a difference in serum zonulin and claudin-5 levels in patients with schizophrenia, which may affect the severity of the disease. Fifty schizophrenia patients and 50 healthy controls were included in this study. The patients were administered the Positive Symptoms Assessment Scale (SAPS) and Negative Symptoms Assessment Scale (SANS) to determine the severity of symptoms. Venous blood samples were collected, and the serum zonulin and claudin-5 levels were measured. The mean serum zonulin levels were significantly increased in patients with schizophrenia when compared to the control group. Serum claudin-5 levels were decreased in the schizophrenia patients when compared to the controls. The present study indicates that zonulin is increased and claudin-5 is decreased in patients with schizophrenia. These findings extend the existing knowledge on the dysregulation of intestinal permeability, especially zonulin, and BBB, especially claudin-5, and show that both proteins may be involved in the etiopathogenesis of schizophrenia.

Prenatal exposure to artificial food colorings alters NMDA receptor subunit concentrations in rat hippocampus.

Exposure to artificial food color additives (AFCAs) has been implicated in the etiology of certain childhood hyperactivity and learning disabilities. N-methyl-D-aspartate receptors and alpha-7 nicotinic acetylcholine receptor (α7 nAChR) are involved in learning and memory. We administered a mixture of AFCAs (erythrosine, ponceau 4R, allura red AC, sunset yellow FCF, tartrazine, amaranth, brilliant blue, azorubine, and indigotine) to female rats during gestation to investigate the effects of prenatal exposure to AFCAs on neurobehavior, spatial learning, and memory in their offspring. We also investigated whether AFCAs modulate NR2A, NR2B, and α7 nAChR protein levels in their offsprings' hippocampi. Although spatial learning and memory were not altered, the offspring of rats exposed to AFCAs exhibited decreased motivation and increased despair-related behavior. NR2A and NR2B protein levels were significantly reduced in female offspring in the experimental group (p < 0.05), whereas α7 nAChR level was not significantly altered. Our results suggest that prenatal exposure to AFCAs may lead to sex-dependent alterations in glutamatergic signaling which may continue into adolescence.

Serum zonulin and claudin-5 levels in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study aimed to investigate serum zonulin and claudin-5 levels of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and healthy controls by controlling the parameters such as age, sex and body mass index (BMI) percentile which are known to affect these parameters. METHOD: A total of 80 treatment-naive children and adolescents with ADHD and 40 healthy volunteer controls aged 8-12 years were enrolled in this study. The severities of ADHD symptoms were assessed via parent- and teacher-rated questionnaires. The severity of anxiety and depression symptoms of the children were assessed by the self-report inventories. Serum levels of zonulin and claudin-5 were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the serum zonulin and claudin-5 levels, an effect that was independent of age, sex and BMI percentile. Significant differences were found between the study groups in terms of serum log-claudin-5 levels. However, there was no significant difference between the study groups in terms of serum zonulin levels. CONCLUSION: These findings provide additional evidence for dysregulation of the blood-brain barrier, especially abnormalities in claudin-5 function, which may be involved in the aetiology of ADHD.Key pointsADHD is one of the most common neurodevelopmental disorders of childhood. Although ADHD is quite common, its aetiology has yet to be fully explained.In recent years, studies on the relationship between intestinal and blood-brain brain barrier permeability and psychiatric disorders have increased.In our study, serum claudin-5 levels were higher in the ADHD group compared to the control group, while serum zonulin levels did not differ between the groups.

Assessment of the effect of pulsed electromagnetic field application on the healing of bone defects in rats with heparin-induced osteoporosis.

Osteoporosis is a systemic skeletal disease characterized by an increase in bone fragility and fracture risk due to low bone mass and deterioration of bone tissue. Application of pulsed electromagnetic fields (PEMF), a non-invasive method with a low complication risk, is known to stimulate bone formation. The present study examines the histomorphometric and biochemical effects of PEMF application on the healing of bone defects in rats with heparin-induced secondary osteoporosis. Briefly, 12-month-old male Sprague-Dawley rats were examined in a prospective, randomized, single-blind study. Osteoporosis was induced by administering a daily dose of 2 IU/g heparin for 33 days. Bone defects were created on the right femur on Day 35. PEMF of an average intensity of 0.8 ± 0.2 mT and a frequency of 7.3 Hz, was applied for 1 h/day, for 28 days following surgery. Bone healing was evaluated by histomorphometric and biochemical analyses. The heparin + PEMF group displayed the largest amount of new bone area (P = .002) and the lowest mean CTx on Day 63 (P = .05). This study demonstrates that heparin administration leads to bone loss and osteoporosis, whereas the application of PEMF decreases this effect.

Serum zonulin and claudin-5 levels in patients with bipolar disorder.

BACKGROUND: The etiology in bipolar disorder has not been fully understanding. There are limited data regarding the relationship between the permeability of intestinal and blood-brain barrier (BBB), and bipolar disorder etiology. Zonulin is regarded as a non-invasive biomarker for intestinal permeability. Claudin-5 is an important part of BBB permeability. In this study, we assumed that there may be a deterioration in serum zonulin and claudin-5 levels in patients with bipolar disorder and this may affect the severity of the disease. METHODS: Forty-one bipolar disorder patients (21 patients in remission and 20 patients with manic episodes) and 41 healthy controls were included in this study. The patients were administered Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) to determine the severity of manic and depressive symptoms, respectively. Venous blood samples were collected, and serum zonulin and claudin-5 levels were measured. RESULTS: The mean serum zonulin and claudin-5 levels in patients were significantly higher than healthy controls. There is no difference zonulin and claudin-5 levels between patients with manic episodes and patients in remission. LIMITATION: This study's small sample size limits the generalization of these outcomes to a larger population. Also, a major limitation of our study is lack of evaluations of gut microbiota in patients with bipolar disorder and controls. CONCLUSION: In conclusion, the current research indicates that zonulin and claudin-5 are increased in patients with bipolar disorder and this finding may contribute to the role of intestinal permeability or BBB in the pathogenesis of bipolar disorder.

Serum zonulin and claudin-5 levels in children with obsessive-compulsive disorder.

Background: Obsessive-compulsive disorder (OCD), a chronically debilitating neuropsychiatric disorder, is characterized by distinctive and recurrent obsessions and/or compulsions. An increasing number of evidence indicates that sophisticated interactions between different neurobiological factors play a part in OCD etiology, but the certain underlying mechanisms are still mainly unknown. The present research aimed to explore whether the concentrations of serum zonulin and claudin-5 vary between OCD patients and healthy controls. The present research also intended to explore whether there is an association between zonulin and claudin-5 concentrations and OCD severity.Methods: Twenty-four (13 boys and 11 girls) OCD patients and 24 (13 boys and 11 girls) healthy controls were included in this study. The clinical severity of the OCD symptoms was evaluated by the Children's Yale-Brown Obsessive-Compulsive Scale and the Maudsley Obsessive-Compulsive Inventory. Participants also filled out the Revised Child Anxiety and Depression Scales-Child Version to determine the anxiety and depression levels of the children. Venous blood samples were collected, and serum zonulin and claudin-5 levels were measured.Results: Serum claudin-5 levels were found to be significantly higher in OCD patient whereas serum zonulin levels were not significantly different between the groups.Conclusions: Taken together with our results, our study suggests that dysregulation of the blood-brain barrier, especially claudin-5, may be involved in the etiology of OCD.

Evaluation of interleukin-1ß level and oxidative status in gingival crevicular fluid during rapid maxillary expansion.

OBJECTIVES: The levels of interleukin-1ß (IL-1ß), nitric oxide (NO), total antioxidant capacity (TAC), and total oxidant status (TOS) in gingival crevicular fluid (GCF) were determined during rapid maxillary expansion (RME) treatment. MATERIALS AND METHODS: Fourteen patients (10-13 years old) were included. A modified hyrax appliance was used for the treatment. After periodontal parameters were recorded, GCF was collected from the first molars at each observation [T1:baseline:14 days after periodontal prophylaxis and instructions; T2:1 day later hyrax inserted, at passive position; T3:1 week later; after the first activation; T4:after 2 × 1/4 activation; T5:after 7 × 1/4 activation; T6:after 14 × 1/4 activation; T7:retention period on the 1 st month; and T8:retention period on the 3rd month]. RESULTS: Although the levels of IL1-ß, NO, and PD increased significantly from T1 to T2, the GI, BOP%, and PI remained unchanged throughout treatment. GCF volume at buccal and palatal surfaces increased significantly from T1 to T4, T6, T7, and T8. The parameters in GCF and TAC levels were not only higher at palatal side in comparison with buccal, but also TOS levels increased at both buccal and palatal sides. CONCLUSIONS: In this study, the differences of oxidative status and IL-1ß levels during RME treatment could be attributable to orthopedic effect of the heavy forces on maxilla and minimal orthodontic forces on teeth applied by the RME apparatus.

The protective effect of pomegranate juice in paracetamol-induced acute hepatotoxicity in rats.

AIM: Being the most commonly used antipyretic and analgesic, paracetamol is one of the most common causes of childhood poisoning in the world and maintains its importance also in our country. Paracetamol poisoning is one of the most common causes of liver failure. This study aimed to investigate if pomegranate juice had protective effect in acute liver toxicity related with paracetamol. MATERIAL AND METHODS: A total of 36 Wistar-Albino rats were divided into four groups as the paracetamol group (3 000 mg/kg paracetamol), the pomegranate juice + paracetamol group (1.5 mL pomegranate juice plus 3 000 mg/kg paracetamol), the pomegranate juice group (1.5 mL pomegranate juice) and the control group (1.5 mL distilled water). Pomegranate juice and distilled water were administered for eight days. Paracetamol was administered on day 8. The level of thiobarbituric acid reactive substances, as an oxidative marker, was measured in the blood and liver tissue on day 9. In addition, liver tissues were evaluated histologically (in terms of increased connective tissue, granular degeneration, mononuclear cell infiltration, necrotic cells and vascular congestion). RESULTS: The liver tissue and blood thiobarbituric acid reactive substances levels were found to be significantly lower in the pomegranate juice + paracetamol group compared to the paracetamol group (p<0.05). Histologically, structural changes related with damage were observed in both the paracetamol group and pomegranate juice + paracetamol group. The extent of damage was statistically significantly lower in the pomegranate juice + paracetamol group (p<0.001). CONCLUSIONS: Our results related with oxidative and histologic evaluation showed that pomegranate juice might have a preventive effect in paracetamol-induced acute liver damage.

Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion.

BACKGROUND: Stroke is one of the most common causes of death and the leading cause of disability in adults. Cerebral ischemia/reperfusion injury causes cerebral edema, hemorrhage, and neuronal death. AIMS: In post-ischemic reperfusion, free radical production causes brain tissue damage by oxidative stress. Pregabalin, an antiepileptic agent was shown to have antioxidant effects. The aim of this study was to evaluate the neuroprotective and antioxidant effects of pregabalin on ischemia and reperfusion in rat brain injury. STUDY DESIGN: Animal experimentation. METHODS: Male Wistar rats weighing (250-300 g) were randomly divided into six groups, each consisting of 6 rats: control (C), pregabalin (P), ischemia (I), pregabalin + ischemia (PI), ischemia + reperfusion (IR) and ischemia + reperfusion + pregabalin (PIR). Rats were initially pre-treated with 50 mg/kg/d pregabalin orally for two days. Then, animals that applied ischemia in I, PI, IR and PIR groups were exposed to carotid clamping for 30 minutes and 20 minutes reperfusion was performed in the relevant reperfusion groups. RESULTS: NR2B receptor levels were significantly lower in the PIR group in comparison to the IR group. In the PIR group, Thiobarbituric acid reactive substance (TBARS) level had statistically significant decrease compared with IR group. Glutathione peroxidase (GSH-PX) levels were also significantly increased in the PIR group compared with I, IR and control groups. In the PI and PIR groups, catalase (CAT) levels were also significantly increased compared with I and IR groups (p=0.03 and p=0.07, respectively). CONCLUSION: Pregabalin may protect the damage of oxidative stress after ischemia + reperfusion. This result would illuminate clinical studies in the future.

The effects of long-term exposure to a 2450 MHz electromagnetic field on growth and pubertal development in female Wistar rats.

The aim of this study was to investigate the effects of a 2450 MHz electromagnetic field (EMF) (wireless internet frequency) on the growth and development of female Wistar rats. The study was conducted on three groups of rats. The prenatal and postnatal groups were exposed to EMF 1 h/day beginning from intrauterine and postnatal periods, respectively. The third group was the sham-exposed group. Growth, nutrition and vaginal opening (VO) were regularly monitored. Serum and tissue specimens were collected at puberty. Histological examinations, total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) measurements in ovary and brain tissues and also immunohistochemical staining of the hypothalamus were performed besides the determination of serum FSH, LH, E2 and IGF-1 values. Birth masses of the groups were similar (p > 0.05). Mass gain per day was significantly lower and the puberty was significantly later in the prenatal group. Brain and ovary TOS and OSI values in the prenatal group were significantly increased (p < 0.05) compared to the control group. Serum LH levels of the prenatal and postnatal groups were increased, although serum FSH, and E2 values did not differ among the groups (p > 0.05). Histological examinations of the specimens revealed no statistically significant difference between the groups (p > 0.05). Exposure to 2450 MHz EMF, particularly in the prenatal period, resulted in postnatal growth restriction and delayed puberty in female Wistar rats. Increased TOS and OSI values in the brain and ovary tissues can be interpreted as a sign of chronic stress induced by EMF. This is the first longitudinal study which investigates the effects of EMF induced by wireless internet on pubertal development beside growth.

Are there any remarkable effects of prenatal exposure to food colourings on neurobehaviour and learning process in rat offspring?

OBJECTIVE: Artificial food colourings and additives (AFCAs) have long been discussed to have adverse effects on cognition and behaviour in children. In this study, our aim was to assess the probable side effects of prenatal exposure to colouring food additives on neurobehaviour and spatial learning process. METHODS: We administered 'no observable adverse effect levels' (NOAELs) of common used AFCAs as a mixture (erythrosine, Ponceau 4R, Allura Red AC, Sunset yellow FCF, tartrazine, Amaranth, Brilliant Blue, Azorubine and Indigotine) to female rats before and during gestation and tested their effects on spatial working memory and behaviour in their offspring. Effects of AFCAs on spatial working memory were evaluated by Morris water maze, behavioural and locomotor effects by open-field and forced-swim tests. RESULTS: Prenatal exposure to commonly used AFCAs had no adverse effects on spatial working memory; however, assessment of interaction of sex and AFCAs on 'latency to locate the visible platform', which was used as a measure of motivation, showed a significant interaction (P < 0.05) on female rats. In addition, AFCAs caused an increase in anxiolytic like effect in the open-field test (P < 0.05) and an increase in mobility time (P < 0.05) in the forced-swim test. We also detected a significant interaction of sex and AFCAs on forced-swim test parameters (P < 0.05). DISCUSSION: These findings indicated that prenatal exposure to NOAELs of AFCAs resulted in implicit adverse effects that caused an increase in motility and a decrease in motivation and anxiety in offspring in sex-related manner.

Do follicular fluid gelatinase levels affect fertilization rates and oocyte quality?

BACKGROUND: Matrix metalloproteinase-2 and -9, known as gelatinases, are considered to be essential for tissue remodelling during the reproductive process. However, their role in reproduction is unclear. AIMS: In the present study, we aimed to investigate the relationship between follicular fluid gelatinase levels and oocyte quality and fertilization, and to compare the activities of gelatinase levels with different drug stimulation protocols. METHODS: We evaluated 60 women with unexplained infertility who underwent in vitro fertilization (IVF) treatment. Thirty patients underwent a gonadotropin-releasing hormone (GnRH) agonist protocol and 30 underwent a GnRH antagonist protocol. Follicular fluid was obtained during oocyte retrieval. Oocyte quality was determined using light microscopy, and oocytes were considered to be fertilized when two pronuclei were present. Gelatinase activities were measured using commercial enzyme-linked immunosorbent assay kits. The study was partially supported by the Scientific Research Unit of Suleyman Demirel University (Protocol Number: 3620-TU1-13), and all procedures were conducted with the approval of the Suleyman Demirel University Local Ethics Board. Statistical analyses of the data were performed using the independent t test, Fisher exact test, Mann-Whitney U test, one-way ANOVA, and posthoc least significant difference. RESULTS: Follicular fluid gelatinase levels were significantly higher for agonist drug administration (p = 0.001), and a positive correlation was observed between matrix metalloproteinase-9 levels and oocyte grade (p = 0.01). Moreover, a positive relationship between matrix metalloproteinase-9 levels and fertilization was observed (p = 0.02). CONCLUSION: Follicular fluid gelatinase activities, particularly MMP-9 activity, might be a predictor of oocyte quality and IVF success.

Effects of maternally exposed food coloring additives on laryngeal histology in rats.

Experimental reports showed carcinogenic effects of artificial food colors and additives (AFCAs) on many organs, including the head and neck region. We aimed to investigate the effect of AFCAs on laryngeal histomorphology and immunohistochemical expression in maternally exposed rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Histopathological and immunohistochemical findings were evaluated in their offspring. Significant decreasing in goblet cell count and cilia loss were observed with AFCAs in maternally exposed rats (p<0.05). Immunohistochemically, the Ki67 index was significantly increased and villin expression was significantly reduced in laryngeal epithelium in the study group (p<0.05), whereas expression of cyclooxygenase type 2, Muc-2, Muc-5AC, p53, and epidermal growth factor receptors did not differ between the groups. This study demonstrated that maternal exposure of AFCAs plays a role in the mucosal defense system and possibly in carcinogenesis.